First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction.

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

Low-Cost EEG Multi-Subject Recording Platform for the Assessment of Students' Attention and the Estimation of Academic Performance in Secondary School.

The level of student attention in class greatly affects their academic performance. Teachers typically rely on visual inspection to react to students' attention in time, but this subjective method leads to inconsistencies across classes. Online education exacerbates the issue as students can turn off cameras and microphones to keep their own privacy. To address this, we present a novel, low-cost EEG-based platform for assessing students' attention and estimating their academic performance. In a study involving 34 secondary school students (aged 14 to 16), participants watched an academic video and answered evaluation questions while their EEG activity was recorded using a commercial headset. The results demonstrate a significant correlation (0.53, p-value = 0.003) between the power spectral density (PSD) of the EEG beta band (12-30 Hz) and students' academic performance. Additionally, there was a notable difference in PSD-beta between high and low academic performers. These findings encourage the use of PSD-beta for the immediate and objective assessment of both the student attention and the subsequent academic performance. The platform offers valuable and objective feedback to teachers, enhancing the effectiveness of both face-to-face and online teaching and learning environments.

Combining aperiodic 1/f slopes and brain simulation: An EEG/MEG proxy marker of excitation/inhibition imbalance in Alzheimer's disease.

INTRODUCTION: Accumulation and interaction of amyloid-beta (Aß) and tau proteins during progression of Alzheimer's disease (AD) are shown to tilt neuronal circuits away from balanced excitation/inhibition (E/I). Current available techniques for noninvasive interrogation of E/I in the intact human brain, for example, magnetic resonance spectroscopy (MRS), are highly restrictive (i.e., limited spatial extent), have low temporal and spatial resolution and suffer from the limited ability to distinguish accurately between different neurotransmitters complicating its interpretation. As such, these methods alone offer an incomplete explanation of E/I. Recently, the aperiodic component of neural power spectrum, often referred to in the literature as the '1/f slope', has been described as a promising and scalable biomarker that can track disruptions in E/I potentially underlying a spectrum of clinical conditions, such as autism, schizophrenia, or epilepsy, as well as developmental E/I changes as seen in aging. METHODS: Using 1/f slopes from resting-state spectral data and computational modeling, we developed a new method for inferring E/I alterations in AD. RESULTS: We tested our method on recent freely and publicly available electroencephalography (EEG) and magnetoencephalography (MEG) datasets of patients with AD or prodromal disease and demonstrated the method's potential for uncovering regional patterns of abnormal excitatory and inhibitory parameters. DISCUSSION: Our results provide a general framework for investigating circuit-level disorders in AD and developing therapeutic interventions that aim to restore the balance between excitation and inhibition.

Supporting the Detection of Early Alzheimer's Disease with a Four-Channel EEG Analysis.

Alzheimer's disease (AD) is the most prevalent form of dementia. Although there is no current cure, medical treatment can help to control its progression. Hence, early-stage diagnosis is crucial to maximize the living standards of the patients. Biochemical markers and medical imaging in combination with neuropsychological tests represent the most extended diagnosis procedure. However, these techniques require specialized personnel and long processing time. Furthermore, the access to some of these techniques is often limited in crowded healthcare systems and rural areas. In this context, electroencephalography (EEG), a non-invasive technique to obtain endogenous brain information, has been proposed for the diagnosis of early-stage AD. Despite the valuable information provided by clinical EEG and high density montages, these approaches are impractical in conditions such as those described above. Consequently, in this study, we evaluated the feasibly of using a reduced EEG montage with only four channels to detect early-stage AD. For this purpose, we involved eight clinically diagnosed AD patients and eight healthy controls. The results we obtained reveal similar accuracies ([Formula: see text]-value[Formula: see text]0.66) for the reduced montage (0.86) and a 16-channel montage (0.87). This suggests that a four-channel wearable EEG system could be an effective tool for supporting early-stage AD detection.

Powering Electronic Implants by High Frequency Volume Conduction: In Human Validation.

OBJECTIVE: Wireless power transfer (WPT) is used as an alternative to batteries to accomplish miniaturization in electronic medical implants. However, established WPT methods require bulky parts within the implant or cumbersome external systems, hindering minimally invasive deployments and the development of networks of implants. As an alternative, we propose a WPT approach based on volume conduction of high frequency (HF) current bursts. These currents are applied through external electrodes and are collected by the implants through two electrodes at their opposite ends. This approach avoids bulky components, enabling the development of flexible threadlike implants. METHODS: We study in humans if HF (6.78 MHz) current bursts complying with safety standards and applied through two textile electrodes strapped around a limb can provide substantial powers from pairs of implanted electrodes. RESULTS: Time averaged electric powers obtained from needle electrodes (diameter = 0.4 mm, length = 3 mm, separation = 30 mm) inserted into arms and lower legs of five healthy participants were 5.9 ± 0.7 mW and 2.4 ± 0.3 mW respectively. We also characterize the coupling between the external system and the implants using personalized two-port impedance models generated from medical images. CONCLUSIONS: The results demonstrate that innocuous and imperceptible HF current bursts that flow through the tissues by volume conduction can be used to wirelessly power threadlike implants. SIGNIFICANCE: This is the first time that WPT based on volume conduction is demonstrated in humans. This method overcomes the limitations of existing WPT methods in terms of minimal invasiveness and usability.

Wireless networks of injectable microelectronic stimulators based on rectification of volume conducted high frequency currents.

Objective.To develop andin vivodemonstrate threadlike wireless implantable neuromuscular microstimulators that are digitally addressable.Approach.These devices perform, through its two electrodes, electronic rectification of innocuous high frequency current bursts delivered by volume conduction via epidermal textile electrodes. By avoiding the need of large components to obtain electrical energy, this approach allows the development of thin devices that can be intramuscularly implanted by minimally invasive procedures such as injection. For compliance with electrical safety standards, this approach requires a minimum distance, in the order of millimeters or a very few centimeters, between the implant electrodes. Additionally, the devices must cause minimal mechanical damage to tissues, avoid dislocation and be adequate for long-term implantation. Considering these requirements, the implants were conceived as tubular and flexible devices with two electrodes at opposite ends and, at the middle section, a hermetic metallic capsule housing the electronics.Main results.The developed implants have a submillimetric diameter (0.97 mm diameter, 35 mm length) and consist of a microcircuit, which contains a single custom-developed integrated circuit, housed within a titanium capsule (0.7 mm diameter, 6.5 mm length), and two platinum-iridium coils that form two electrodes (3 mm length) located at opposite ends of a silicone body. These neuromuscular stimulators are addressable, allowing to establish a network of microstimulators that can be controlled independently. Their operation was demonstrated in an acute study by injecting a few of them in the hind limb of anesthetized rabbits and inducing controlled and independent contractions.Significance.These results show the feasibility of manufacturing threadlike wireless addressable neuromuscular stimulators by using fabrication techniques and materials well established for chronic electronic implants. Although long-term operation still must be demonstrated, the obtained results pave the way to the clinical development of advanced motor neuroprostheses formed by dense networks of such wireless devices.

Floating EMG sensors and stimulators wirelessly powered and operated by volume conduction for networked neuroprosthetics.

BACKGROUND: Implantable neuroprostheses consisting of a central electronic unit wired to electrodes benefit thousands of patients worldwide. However, they present limitations that restrict their use. Those limitations, which are more adverse in motor neuroprostheses, mostly arise from their bulkiness and the need to perform complex surgical implantation procedures. Alternatively, it has been proposed the development of distributed networks of intramuscular wireless microsensors and microstimulators that communicate with external systems for analyzing neuromuscular activity and performing stimulation or controlling external devices. This paradigm requires the development of miniaturized implants that can be wirelessly powered and operated by an external system. To accomplish this, we propose a wireless power transfer (WPT) and communications approach based on volume conduction of innocuous high frequency (HF) current bursts. The currents are applied through external textile electrodes and are collected by the wireless devices through two electrodes for powering and bidirectional digital communications. As these devices do not require bulky components for obtaining power, they may have a flexible threadlike conformation, facilitating deep implantation by injection. METHODS: We report the design and evaluation of advanced prototypes based on the above approach. The system consists of an external unit, floating semi-implantable devices for sensing and stimulation, and a bidirectional communications protocol. The devices are intended for their future use in acute human trials to demonstrate the distributed paradigm. The technology is assayed in vitro using an agar phantom, and in vivo in hindlimbs of anesthetized rabbits. RESULTS: The semi-implantable devices were able to power and bidirectionally communicate with the external unit. Using 13 commands modulated in innocuous 3 MHz HF current bursts, the external unit configured the sensing and stimulation parameters, and controlled their execution. Raw EMG was successfully acquired by the wireless devices at 1 ksps. CONCLUSIONS: The demonstrated approach overcomes key limitations of existing neuroprostheses, paving the way to the development of distributed flexible threadlike sensors and stimulators. To the best of our knowledge, these devices are the first based on WPT by volume conduction that can work as EMG sensors and as electrical stimulators in a network of wireless devices.

Interleaved intramuscular stimulation with minimally overlapping electrodes evokes smooth and fatigue resistant forces.

OBJECTIVE: It is known that multi-site interleaved stimulation generates less muscle fatigue compared to single-site synchronous stimulation. However, in the limited number of studies in which intramuscular electrodes were used, the fatigue reduction associated with interleaved stimulation could not consistently be achieved. We hypothesize that this could be due to the inability to place the intramuscular electrodes used in interleaved stimulation in locations that minimize overlap amongst the motor units activated by the electrodes. Our objective in the present study was to use independent intramuscular electrodes to compare fatigue induced by interleaved stimulation with that generated by synchronous stimulation at the same initial force and ripple. APPROACH: In the medial gastrocnemius muscle of an anesthetized rabbit (n = 3), ten intramuscular hook wire electrodes were inserted at different distances from the nerve entry. Overlap was measured using the refractory technique and only three electrodes were found to be highly independent. After ensuring that forces obtained by both stimulation modalities had the same ripple and magnitude, fatigue induced during interleaved stimulation across three independent distal electrodes was compared to that obtained by synchronously delivering pulses to a single proximal electrode. MAIN RESULTS: Contractions evoked by interleaved stimulation exhibited less fatigue than those evoked by synchronous stimulation. Twitch force recruitment curves collected from each of the ten intramuscular electrodes showed frequent intermediate plateaus and the force value at these plateaus decreased as the distance between the electrode and nerve entry increased. SIGNIFICANCE: The results indicate that interleaved intramuscular stimulation is preferred over synchronous intramuscular stimulation when fatigue-resistant and smooth forces are desired. In addition, the results suggest that the large muscle compartments innervated by the primary intramuscular nerve branches give rise to progressively smaller independent compartments in subsequent nerve divisions.

Portable System for Real-Time Detection of Stress Level.

Currently, mental stress is a major problem in our society. It is related to a wide variety of diseases and is mainly caused by daily-life factors. The use of mobile technology for healthcare purposes has dramatically increased during the last few years. In particular, for out-of-lab stress detection, a considerable number of biosignal-based methods and systems have been proposed. However, these approaches have not matured yet into applications that are reliable and useful enough to significantly improve people's quality of life. Further research is needed. In this paper, we propose a portable system for real-time detection of stress based on multiple biosignals such as electroencephalography, electrocardiography, electromyography, and galvanic skin response. In order to validate our system, we conducted a study using a previously published and well-established methodology. In our study, ten subjects were stressed and then relaxed while their biosignals were simultaneously recorded with the portable system. The results show that our system can classify three levels of stress (stress, relax, and neutral) with a resolution of a few seconds and 86% accuracy. This suggests that the proposed system could have a relevant impact on people's lives. It can be used to prevent stress episodes in many situations of everyday life such as work, school, and home.

Blue lighting accelerates post-stress relaxation: Results of a preliminary study.

Several authors have studied the influence of light on both human physiology and emotions. Blue light has been proved to reduce sleepiness by suppression of melatonin secretion and it is also present in many emotion-related studies. Most of these have a common lack of objective methodology since results and conclusions are based on subjective perception of emotions. The aim of this work was the objective assessment of the effect of blue lighting in post-stress relaxation, in comparison with white lighting, by means of bio-signals and standardized procedures. We conducted a study in which twelve healthy volunteers were stressed and then performed a relaxation session within a chromotherapy room with blue (test group) or white (control group) lighting. We conclude that the blue lighting accelerates the relaxation process after stress in comparison with conventional white lighting. The relaxation time decreased by approximately three-fold (1.1 vs. 3.5 minutes). We also observed a convergence time (3.5-5 minutes) after which the advantage of blue lighting disappeared. This supports the relationship between color of light and stress, and the observations reported in previous works. These findings could be useful in clinical and educational environments, as well as in daily-life context and emerging technologies such as neuromarketing. However, our study must be extended to draw reliable conclusions and solid scientific evidence.

EEG topographies provide subject-specific correlates of motor control.

Electroencephalography (EEG) of brain activity can be represented in terms of dynamically changing topographies (microstates). Notably, spontaneous brain activity recorded at rest can be characterized by four distinctive topographies. Despite their well-established role during resting state, their implication in the generation of motor behavior is debated. Evidence of such a functional role of spontaneous brain activity would provide support for the design of novel and sensitive biomarkers in neurological disorders. Here we examined whether and to what extent intrinsic brain activity contributes and plays a functional role during natural motor behaviors. For this we first extracted subject-specific EEG microstates and muscle synergies during reaching-and-grasping movements in healthy volunteers. We show that, in every subject, well-known resting-state microstates persist during movement execution with similar topographies and temporal characteristics, but are supplemented by novel task-related microstates. We then show that the subject-specific microstates' dynamical organization correlates with the activation of muscle synergies and can be used to decode individual grasping movements with high accuracy. These findings provide first evidence that spontaneous brain activity encodes detailed information about motor control, offering as such the prospect of a novel tool for the definition of subject-specific biomarkers of brain plasticity and recovery in neuro-motor disorders.

Stress Assessment by Prefrontal Relative Gamma.

Stress assessment has been under study in the last years. Both biochemical and physiological markers have been used to measure stress level. In neuroscience, several studies have related modification of stress level to brain activity changes in limbic system and frontal regions, by using non-invasive techniques such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). In particular, previous studies suggested that the exhibition or inhibition of certain brain rhythms in frontal cortical areas indicates stress. However, there is no established marker to measure stress level by EEG. In this work, we aimed to prove the usefulness of the prefrontal relative gamma power (RG) for stress assessment. We conducted a study based on stress and relaxation periods. Six healthy subjects performed the Montreal Imaging Stress Task (MIST) followed by a stay within a relaxation room while EEG and electrocardiographic signals were recorded. Our results showed that the prefrontal RG correlated with the expected stress level and with the heart rate (HR; 0.8). In addition, the difference in prefrontal RG between time periods of different stress level was statistically significant (p < 0.01). Moreover, the RG was more discriminative between stress levels than alpha asymmetry, theta, alpha, beta, and gamma power in prefrontal cortex. We propose the prefrontal RG as a marker for stress assessment. Compared with other established markers such as the HR or the cortisol, it has higher temporal resolution. Additionally, it needs few electrodes located at non-hairy head positions, thus facilitating the use of non-invasive dry wearable real-time devices for ubiquitous assessment of stress.